MCM Final - DNA Damage and Repair

Question 0

depurination

Answer 0

removal of a purine

- remove base from backbone
- link to deoxyribose hydrolyzed

Question 1

spontaneous lesions

Answer 1

small chemical modification (single base pair)

Question 2

deamination

Answer 2

cytosine changed to uracil

Question 3

bulky lesions

Answer 3

cause a large change in DNA strand

Question 4

covalent linkage

Answer 4

bulky lesion caused by oxidative species, UV light, or carcinogens
-cause a change in DNA helix structure

Question 5

copy errors

Answer 5

DNA polymerase incorrectly adds base pair

Question 6

mutagen

Answer 6

agent (physical or chemical) that causes an alteration in DNA

Question 7

base analog

Answer 7

mutagen structurally resembles purine or pyrimidine and inserts into DNA strand

Question 8

intercalating agent

Answer 8

mutagen that insert between double helix

usually flat with multiple rings

cause stretching of double helix and DNA polymerase adds extra bases opposite to it

Question 9

direct acting agent

Answer 9

chemically react with DNA directly

Question 10

indirect acting agent

Answer 10

require metabolic conversion before actively altering DNA

Question 11

cytochrome p-450

Answer 11

mechanism by which an indirect acting agent is converted into a mutagen that can alter the DNA

Question 12

UV radiation

Answer 12

shorter wavelengths - more energy - more damage

UV-A (320-400nm) - induces oxidative damage
UV-B (280-320nm) - induces dimers between pyrimidines (C or T)
UV-C (180-290nm) - doesn’t make it through ozone

Question 13

ionizing radiation

Answer 13

causes ionization

- loss of electron
- unstable reactive radical

Question 14

alpha particle

Answer 14

helium nuclei

Question 15

beta particle

Answer 15

high speed electron

Question 16

damage due to ionizing radiation?

Answer 16

single strand break
double strand break **
base damage
cross linking

Question 17

base excision repair

Answer 17

repair spontaneous lesions (single base pair)

1 DNA glycosylase scans DNA and removes damaged bases
2 AP endonuclease cuts phosphodiester backbone where empty base spot is
3 DNA polymerase adds nucleotide correctly
4 DNA ligase seals nick

Question 18

DNA glycosylase

Answer 18

in base excision repair

- scans DNA for damaged bases and removes them
- leaves backbone in tact

Question 19

AP endonuclease

Answer 19

in base excision repair

-cleaves phosphodiester bond where DNA glycosylase has removed a base pair

Question 20

nucleotide excision repair

Answer 20

repairs bulky lesions (larger)

1 multienzyme complex scans for distorted DNA helix
-cleaves phosphodiester backbone on either side of distortion
2 DNA helicase removes the single strand cleaved out
3 DNA polymerase adds nucleotides
4 DNA ligase seals the nick

Question 21

multienzyme complex

Answer 21

in nucleotide excision repair

-scans for distorted DNA helix and cleaves phosphodiester bonds on each side of distortion

Question 22

mismatch repair

Answer 22

correct DNA mismatches of DNA polymerase

follow behind replication
-recognize strand breaks (okazaki fragments - lagging)
MutS and MutL bind to mismatched base
-direct excison of DNA between the single strand break and mismatch

Question 23

3’ to 5’ exonuclease activity

Answer 23

proofreading during replication

-by DNA polymerase

Question 24

back-up polymerases

Answer 24

when 3' to 5' exonuclease doesn't work less accurate - take guess at what sequence should be

Question 25

transcription coupled repair

Answer 25

RNA polymerase II stalls at lesion -on template strand only directs repair machinery to the site CSB recognizes stalled RNA polymerase II TFIIH remodels RNA polymerase II XPG cuts DNA Lesion repaired and polymerase restarts

Question 26

double strand break causes

Answer 26

radiaton, errors, and oxidation

Question 27

non-homologous end joining

Answer 27

less accurate, ends brought together and ligated | -loss of nucleotides

Question 28

homologous recombination

Answer 28

more accurate | -sister chromatids used as a template

Question 29

Process of non-homologous end joining

Answer 29

1 Ku70/80 recognizes free double strane ends 2 recruits DNA-PK which acts as a kinase to recruit ligase 3 DNA ligase ligates the ends

Question 30

Ku 70/80

Answer 30

recognize free double strand break during nonhomologous end joining

Question 31

DNA-PK

Answer 31

recruited to double strand break by Ku70/80 during nonhomologous end joining -act as kinase to recruit DNA ligase

Question 32

Process of Homologous Recombination

Answer 32

1 double break strands are broken to yield 3' single strand ends 2 Rad51 pairs with 3' overhang -causes it to bind with sister chromatid 3 DNA synthesis occurs using sister chromatid as a template (holliday junction is formed, but then resolved) 4 newly synthesized DNA strand then used as template for other broken strand 5 DNA ligation

Question 33

Rad51

Answer 33

binds free 3' ends of double strand breaks during homologous recombination -allows the end to bind with sister chromatid as template

Question 34

DNA damage checkpoints

Answer 34

G1 to S Slow S S to M

Question 35

ATM protein

Answer 35

generates intracellular signals in response to spontaneous DNA damage associates with damage and phosphorylation of downstream kinases -kinases then act on target proteins -p53 - target usually bound by Mdm2 (destroyed) -when phosphorylated - stimulate synthesis of p21 -bind G1/S-Cdk or S-Cdk complex and inhibit them Chk1 and Chk2 - block activation of M-Cdk

Question 36

p53

Answer 36

inhibited when dephosphorylated by association with Mdm2 - when phosphorylated: - stimulates transcription of p21 - which binds G1/S-Cdk or S-Cdk and inhibit them

Question 37

Mdm2

Answer 37

bind p53 targeting it for destruction

Question 38

p21

Answer 38

its transcription activated by p53 - binds G1/S-Cdk or S-Cdk and inhibits them - arrest of cell cycle entry

Question 39

Chk1 and Chk2

Answer 39

block activation of M-Cdk

Question 40

Telomere shortening triggers what?

Answer 40

activation of p53 | -causes cell cycle arrest